In rotenone and 6-OHDA rat models of Parkinson's, systemic uridine (30 mg/kg for 28 days) reduced peripheral lymphocyte SDH and LDH hyperactivity and serum lipid peroxides, and this effect was abolished by the mitoKATP inhibitor 5-hydroxydecanoate, implicating mitoKATP-mediated mitochondrial…

Suggests a repurposable metabolite (uridine) that targets mitoKATP to modulate mitochondrial function and systemic oxidative biomarkers in PD models, providing a mechanistic, mitochondria-focused lead and peripheral biomarker strategy for translational follow-up despite lack of direct CNS…

We investigated the effect of the nucleoside uridine on the activities of key enzymes of oxidative phosphorylation (succinate dehydrogenase, SDH) and glycolysis (lactate dehydrogenase, LDH) in peripheral blood lymphocytes, and on oxidative metabolism in the blood serum of rats in the rotenone and 6-OHDA models of Parkinson's disease. Both models were characterized by increased SDH and LDH activities in lymphocytes and accumulation of lipid peroxides in the blood serum. Injections of uridine, affecting the functioning of mitochondrial K-ATP channel (mitoKATP), to animals at a dose of 30 mg/kg body weight for 28 days mitigated SDH and LDH hyperactivation in lymphocytes and reduced the serum level of LPO products. Specific mitoKATP inhibitor 5-hydroxydecanoate (5 mg/kg) eliminated the effect of uridine. The role of mitoKATP in the protective effect of uridine in a model of Parkinson's disease is discussed.